E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
dose ranging phase III study to assess AIN457 versus placebo in inducing and maintaining uveitis suppression in adults with active, non-infectious, intermediate, posterior or panuveitis requiring immunosuppression |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10046851 |
E.1.2 | Term | Uveitis |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of three dose regimens of subcutaneous AIN457 compared to placebo when administered as an adjunctive therapy to standard-of-care immunosuppressive medications for inducing quiescence and maintaining quiescence during the withdrawal of concomitant immunosuppressive therapy in adults with active, non-infectious, intermediate uveitis, posterior uveitis or panuveitis. |
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E.2.2 | Secondary objectives of the trial |
To determine if treatment with subcutaneous AIN457 can reduce or eliminate the need for standard of care immunosuppressive medications • To assess the safety of targeted IL-17 inhibition with AIN457 in patients with active uveitis affecting the posterior segment requiring standard-of-care immunosuppression • To evaluate the effect of subcutaneous AIN457 on macular edema, visual acuity, and quality of life when used as an adjunctive immunomodulatory therapy to standard-of-care immunosuppressive treatment
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients eligible for inclusion in this study have to fulfill all of the following criteria: 1. Male and female subjects ≥18 years of age. Where relevant, parents will also sign the informed consent according to local laws and regulations. 2. Patients with diagnosis of chronic non-infectious intermediate uveitis, posterior uveitis or panuveitis in at least one eye 3. Evidence of active intermediate, posterior or panuveitis (grade ≥ 2+ vitreous haze with or without the presence of anterior chamber cells) at screening and baseline in at least one eye 4. Requirement for any of the following immunosuppressive therapies for the treatment or prevention of uveitis • Prednisone or equivalent ≥10 mg daily at any time within the past 3 months • ≥1 periocular injection or ≥1 intravitreal corticosteroid injection (e.g. triamcinolone) in the study eye within the past 6 months (the last injection must not have been given 6 weeks prior to screening) • Treatment with either cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, mycophenolic acid, methotrexate at any time within the past 3 months. (Patients treated with chlorambucil or cyclophosphamide within the past 5 years are ineligible for the study) • Patients not meeting the above specified criteria for immunosuppressive therapies are eligible for enrollment if they are intolerant to systemic immunosuppressive therapy as determined by the study investigator 5. Patient must be able to understand and communicate with the investigator and comply with the requirements of the study and must give a written, signed and dated informed consent before any study assessment is performed
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E.4 | Principal exclusion criteria |
Patients fulfilling any of the following criteria are not eligible for inclusion in this study: Ocular concomitant conditions/disease, specified in the protocol, page 26 Ocular treatments, specified in the protocol, page 26 Systemic conditions or treatments, specified in the protocol, page 26 Compliance/Administrative, specified in the protocol, page 27 |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficay variable is the mean change in vitreous haze grade in the study eye from baseline to week 28 Secondary endpoints: The key secondary efficacy variable is the change in immunosuppressive medication score from baseline to Week 28. The following are the other efficacy endpoints: • Proportion of responders with no recurrence of active intermediate, posterior, or panuveitis in the study eye at 28 weeks. Responders are defined as patients achieving quiescence (≤ 0.5+ anterior chamber cell grade and ≤ 0.5+ vitreous haze grade) in the study eye during 28 weeks. Responders may not experience any of the following during the 28- week treatment period: • A ≥ 2 step increase in vitreous haze with or without an increase in anterior chamber cell grade in the study eye at any time during the study • A decrease in best corrected visual acuity ≥ 10 ETDRS letters compared to baseline or the previous visit attributed to ocular inflammation in the study eye. • An increase in concomitant immunosuppressive medication for the treatment of active intermediate, posterior or panuveitis for the study eye • Proportion of responders with no recurrence by visit • Mean time to rescue treatment • Proportion of patients receiving rescue therapy by visit • Mean time from achieving first quiescence to recurrence within a 16 week period • Mean time from achieving first quiescence to ≥2 step increase in vitreous haze • Mean time from achieving first quiescence to a decrease in best corrected visual acuity ≥ 10 ETDRS letters from baseline or prior study visit attributed to ocular inflammation in the study eye • Mean time to response and mean duration of response • Mean immunosuppressive score from baseline to 28 weeks • Mean change in best corrected visual acuity from baseline to 28 weeks • Mean change in foveal thickness from baseline to 28 weeks as measured by optical coherence tomography (OCT) • Change in Quality of Life/Patient reported outcome assessments from baseline at 28 weeks • Proportion of patients with >15 ETDRS letter gains or loss of visual acuity at 28 weeks • Mean change in anterior chamber cell grade from baseline to 28 weeks • Mean change in vitreous haze grade from baseline to 28 weeks • Assessment of the primary and secondary endpoints in the affected fellow non-study eye and per patient • Fundus photographs and fluorescein angiograms will be collected for later exploratory evaluation of change in leakage and manifestations of intraocular inflammation in the retina and choroid
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Patient will have completed the core study after having received a maximum of 26 weeks ± 3 days of study medication and completed of all the scheduled study assessments and procedures up to and including Visit 17. The study will be complete when all randomized patients have completed their final visit.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 9 |